Synthesis and biological activity of high-affinity retinoic acid receptor antagonists

This article reports the synthesis and biological activity of new high affi nity retinioic acid receptor (RAR) antagonists. The effect of introducing h eteroatoms in the bicyclic ring system of the potent dihydronaphthalene RAR antagonist 8, and the variation of the pendant aromatic group on the abili ty of these compounds to function as RAR antagonists is discussed. The use of binding, transcriptional, and in vivo assays revealed that the 2,2-dimet hylthiochromene analogue 59, and the 2,2-dimethylchromene derivative 85, we re the most effective in blocking retinoid agonist induced activity. (C) 19 99 Elsevier Science Ltd. All rights reserved.